Planar 2.2 paracyclophane

In addition to the organophosphine catalyst 54, several useful chiral phosphines have been developed by other groups. The Hou group constructed a planar [2.2] paracyclophane phosphine 55 that catalyzed the allylic substitution of a series of MBH carbonates and acetates with phthalimide to afford products with variable results (Scheme 11.42) [123]. Screening of the solvents revealed that THF and DME are the best one in terms of both reactivity and enantioselectivity. 

In 2004, Bolm et al. reported the use of chiral iridium complexes with chelating phosphinyl-imidazolylidene ligands in asymmetric hydrogenation of functionalized and simple alkenes with up to 89% ee [17]. These complexes were synthesized from the planar chiral [2.2]paracyclophane-based imida-zolium salts 74a-c with an imidazolylidenyl and a diphenylphosphino substituent in pseudo ortho positions of the [2.2]paracyclophane (Scheme 48). Treatment of 74a-c with t-BuOLi or t-BuOK in THF and subsequent reaction of the in situ formed carbenes with [Ir(cod)Cl]2 followed by anion exchange with NaBARF afforded complexes (Rp)-75a-c in 54-91% yield. The chela-... 

Some other enantioselective approaches have been attempted, still with moderate enantioselectivities, by making use of in situ systems containing a chiral NHC precursor. Luo and co-workers reported on the use of the bidentate chiral imidazo-lium salt 16, derived from L-proUne, in combination with [RhCia-COCcod)], leading to an enantiometic excess of around 20% [30]. The use of chiral imidazolium salt 17 in combination with [RhCl(CH2=CHj)j]j by Aoyama afforded slightly better ee (Fig. 7.3) [31 ]. So far, Bohn and co-workers have obtained the best enantioselectivities (up to 38% ee) for the catalytic addition of phenylboronic acid to aromatic aldehydes by using planar chiral imidazolium salts 18, derived from paracyclophane, in combination with [Rh(OAc)2]2 [32]. 

In order to study the role of the [2.2]paracyclophane-type planar chirality in asymmetric induction, Hou et al. have developed the synthesis of novel S/N-... 

The substance 4,12-dibromo[2.2]paracyclophane is the key intermediate en route to several functional C2-symmetric planar-chiral 4,12-disubstituted[2.2]paracydo-phanes. Braddock and coworkers have shown that this important intermediate can be obtained by microwave-assisted isomerization of 4,16-dibromo[2.2]paracydo-phane, itself readily prepared by bromination of [2.2]paracyclophane (Scheme 6.88) [182], By performing the isomerization in N,N-dimethylformamide as solvent (microwave heating at 180 °C for 6 min), in which the pseudo-para isomer is insolu-... 

The UV spectra of 4,5,7,8-tetrafluoro[2.2]paracyclophane (26) 18> and of the octafluoro compound 27 54> reveal the close relationship of these compounds to unsubstituted [2.2]paracyclophane (2). The absorption bands occurring between 286 and 291 nm, like those in the spectra of 2 can be attributed to deformation away from planarity of the aromatic rings. Compared with the fluorine-substituted open-chain analogs, these absorption bands are likewise bathochromically shifted by about 25 nm. 

Pye and Rossen have developed a planar chiral bisphosphine ligand, [2.2]PHANE-PHOS, based on a paracyclophane backbone (Scheme 1.6) [69]. Moreover, the ortho-phenyl substituted NAPHOS ligand, Ph-o-NAPHOS, has been successfully applied for the rhodium-catalyzed hydrogenation of a-dehydroamino acid derivatives [70]. 

Optically active chochins were prepared by the Hofmann route 641 starting from (i )(—)-4-methyl[2.2]paracyclophane (38) with known chirality 54,67) (see 2.9.). Introduction of the trimethyl-ammoniomethyl group (via acetylation and subsequent transformations) afforded (—)-39 which was then cross-coupled with the ammonium base 36 to give a mixture of [2.2]paracyclophane and the levorotatory[3] and [4]chochins (40,43) with ( )-chirality in these cases the descriptors (/ ) and (5) specify the planar chirality of the inner rings(s) as shown in Fig. 2, in accordance with the rules presented in Section 1.2. 

For [2.2]paracyclophane-4-carboxylic acid (25) as (—)(R) This result has been mentioned in a footnote in Ref. 1011 but seems never to have been published (see also Ref. 61). The chirality of this acid was correlated via its ( )-aldehyde with a levo-rotatory hexahelicene derivative which, according to the paracyclophane moiety at the terminal, had to adopt (A/)-helicity. Its chiroptical properties are comparable to those of hexahelicene itself101. For the (—)-bromoderivative of the latter the (A/)-helicity was established by the Bijvoet-method 102). In a later study, (—)para-cyclophane-hexahelicene prepared from (—)-l,4-dimethylhexahelicene with known chirality (which in turn was obtained with approximately 12% enantiomeric purity by asymmetric chromatography) confirmed these results. It should be mentioned that [2.2]paracyclophane-4-carboxylic acid (25) was the first planar chiral cyclophane whose chirality was determined 1041 (see also Ref.54 ). The results justmentioned confirmed the assignment (+)( ). 

The development of ferrocene 9 was part of our studies on planar-chiral compounds, which also involved the synthesis of other scaffolds such as chromium-tricarbonyl arenes [15], sulfoximidoyl ferrocenes [16], and [2.2]paracyclophanes [17]. In aryl transfer reactions, however, ferrocene 9 proved to be the best catalyst in this series, and it is still used extensively today. 

The element of planar chirality plays a pivotal role in many modern ligand systems. The particularly huge success of ferrocenyl ligands has not been matched by any other chiral backbone to date. Metallocene and metal-arene-based ligand backbones exhibit the common feature that they become planar chiral only upon addition of (at least) two substituents on one ring fragment. [2.2]Paracyclophanes, however, need only one substituent (Fig. 2.1.3.1) to be chiral. 

The use of planar-chiral [7] and central-chiral ligands based on paracyclophane systems was still a relatively unexplored frontier, with notable exceptions in the reactions examined by the Rozenberg group [8] and the Berkessel group [9]. 

The well-established planar- and central-chiral ferrocenyl ligands have shown high activity and selectivity in the reaction. However, to the best of our knowledge, these ligands have no central-chiral equivalent with similar bond length and bond angles. In comparison, the [2.2]paracyclophane structure creates central-chiral structures with similar properties, which offer the great opportunity to study its influence on different kinds of chiral elements. 

S. Erase, Planar chiral ligands based on [2.2]paracyclophanes, in Asymmetric Synthesis - The Essentials (Eds. M. Christmann, S. Erase), Wiley-VCH, Weinheim, 2006. 

The inter-ring separation in [4.4] paracyclophane has been calculated to be 3.73 A, assuming normal bond angles and planar benzene rings. At this distance, there is no ground-state overlap, and the UV absorbance does not extend past 280 nm. Nevertheless, the peak of the excimer fluorescence intensity of [4.4] paracyclophane is red-shifted 1900 cm"1 relative to the peak of the solution excimer of toluene at 31,300 cm-1. Neither the excimer lifetime nor the excimer fluorescence response function have been reported for any of the exrimer-forming paracyclophanes, so little is known about the kinetics of excimer formation in these compounds. 

Figure 32. Planar presentations of the graphs of [m][n]paracyclophane and triplelayered cyclophane.

A chiral [2.2]paracyclophane bearing a /3-hydroxyamino side-chain catalyses enan-tioselective reaction with aromatic and a -unsaturated aldehydes.220 Comparison with simpler catalysts suggests that the new one exhibits cooperative effects between planar and central chiralities. 

Enantioselective addition of diethylzinc to aldehydes has been catalyzed by diastere-omeric monosubstituted [2.2]paracyclophane-based A,0-ligands.117 A remarkable cooperative effect of planar and central chiralities has been observed. 

In addition, chiral dendrimers (see Section 4.2) can be resolved with the aid of HPLC into their enantiomers, if the silica gel material used as stationary phase has optically active substances bound to its surface [9]. Since the chiral stationary phase (CSP) [10] undergoes different intensities of interaction with the enantiomeric dendrimers, they are retained to different degrees, and in the ideal case two completely separated (baseline separated) peaks are obtained. This separation technique was successfully applied inter alia to racemic mixtures of planar-chiral dendro[2.2]paracyclophanes, cycloenantiomeric dendro[2] rotaxanes, topologically chiral dendro[2]catenanes [11] as well as topologically chiral, dendritically substituted molecular knots (knotanes) [12] (Section 4.2.3). 

Bidentate oxazoline-imidazolylidene ligands, in which both units are linked by a chiral paracyclophane, have been studied in Bolm s group [129]. In this case, the planar chirality of the pseudo-orfho-paracyclophane is combined with the central chirality of an oxazoline (Scheme 48). Compounds 70 were tested in the asymmetric hydrogenation of olefins displaying moderate selectivity (ee s of up to 46% for dimethylitaconate in the presence of 70b). 

Paracyclophane[4,5-(/]oxazol-2(3/7)-one (152) exhibiting planar chirality has been used as chiral auxiliary in asymmetric Diels-Alder (DA) and Michael reactions via a,P-... 

Paracyclophanes have been recognized for some time as interesting structures for stereochemical studies and for unusual intra- and intermolecular 7r-electron interactions.4-7 The non-planar, boatlike benzene rings8 of these compounds have attracted the attention of numerous synthetic organic chemists4-7 as well as theoreticians9,10 and spectroscopists.7,11... 

Apart from the role of cyclophanes as a model system for studying the electronic interaction between the aromatic moieties, chiral [2.2]paracyclophanes have also been utilized as planar chiral ligands in asymmetric catalysis. Recent advances and applications in this area have been reviewed [5, 6]. The synthesis of heterocyclic compounds based on [2.2]paracyclophane architecture, where the long-distance electronic communication and the planar chirality play significant roles in their application, has also been reported recently [7]. Although the preparation and application of chiral cyclophanes in asymmetric synthesis has attracted much attention for a long time, their chiroptical properties, especially the CD spectra, have rarely been paid attention or even completely ignored. 

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